HIV AIDS medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Acquired immune deficiency syndrome (AIDS) is a collection of symptoms and infections resulting from the specific damage to the immune system caused by the human immunodeficiency virus (HIV) in humans,[1] and similar viruses in other species (SIV, FIV, etc.)
Anti-HIV medications (also called antiretrovirals) are grouped into six drug classes according to their mechanism of action. The six classes are as follows:
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs).
- Nucleoside reverse transcriptase inhibitors (NRTIs).
- Protease inhibitors (PIs).
- Fusion inhibitors.
- CCR5 antagonists.
- Integrase inhibitors.
Multidrug regimen has proved to be very beneficial because of reduction in progression to AIDS, opportunistic infections, rate of hospitalizations and deaths. [2]
Goals of therapy
DHHS ART Guidelines present the following goals for therapy:
- Durable suppression of HIV viral load ( to <50 cells/mL ).
- Restoration of normal CD4 cell count.
- Prevention of transmission of the disease.
- Prevention of building of drug resistance.
- Improvement in quality of life of the patient.
Uncontrolled viremia causes inflammation and immune activation, which has an overall effect on cardiovascular, renal and hepatic systems. Controlling viremia also controls these effects.
Anti Retroviral Therapy (ART)
Indications
The DHHS guidelines currently recommend the follwing:
| Symptoms | CD4 count | Treatment |
| Asymptomatic | <500 | Treatment should be offered. |
| Asymptomatic | >500 | Treatment is optional. |
| Symptomatic | Any value | Treatment should be initiated.[3] |
Selection of the regimen
US Department of Health and Human Services (DHHS) have published guidelines for initial ART based on data from randomized controlled trials. Current optimal HAART options consist of combinations (or "cocktails") consisting of at least three drugs belonging to at least two types, or "classes," of antiretroviral agents.
Typical regimens consist of:
- Two nucleoside analogue reverse transcriptase inhibitors (NARTIs or NRTIs) PLUS
- Either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor (NNRTI).
Following regimens are recommended by DHHS:
- A boosted PI: atazanavir (ATV/r) once daily or darunavir (DRV/r) once daily plus 2 NRTIs OR
- An integrase inhibitor, raltegravir (400 mg twice daily) with 2 NRTIs.
The recommended NRTI coformulation is TDF/FTC in all of the above combinations. In treatment-naive patients, four drug regimen is not found to be more efficacious than three-drug regimens and is associated with more adverse events.[4][5]
Treatment-naive patients
The DHHS Guidelines recommend that therapy should be initiated in the following patient populations:
- Patients with history of an AIDS-defining illness or with a CD4 count of less than 350/µL.
- Pregnant women with HIV infection.
- Patients with HIV-associated nephropathy.
- Patients with HIV and hepatitis B virus (HBV) coinfection who require treatment for HBV infection.
Fusion inhibitors (eg, enfuvirtide) are not approved for treatment-naive patients.
Treatment-experienced patients
Treatment failure is defined by the following factors:
- Virologic failure: which is defined as suboptimal viral suppression or loss of suppression (>50 HIV-1 RNA copies/mL).
- Immunologic failure : which is defined as failure to achieve or maintain CD4 cell count recovery despite effective viral suppression.
- Development of new opportunistic infections or neoplasms despite apparent CD4 count recovery.
Initial HIV therapy
NNRTI, PI, or integrase inhibitor-based regimen in combination with dual NRTIs is considered as an initial HIV therapy. Currently, CCR5 inhibitors are not recommended due to lack of sufficient published data. The particular choice of agent depends on the following factors:
- Side effect profiles.
- Comorbidities in patient.
- Potential drug interactions.
- Allergy history.
- Pregnancy status.
- Patient convenience.
Highly Active Anti-Retroviral Therapy
- Current treatment for HIV infection consists of highly active antiretroviral therapy, or HAART.[6] This has been highly beneficial to many HIV-infected individuals since its introduction in 1996 when the protease inhibitor-based HAART initially became available.
- In developed countries where HAART is available, doctors assess the viral load, rapidity in CD4 decline, and patient readiness while deciding when to recommend initiating treatment.[7]
- In the absence of HAART, progression from HIV infection to AIDS occurs at a median of between nine to ten years and the median survival time after developing AIDS is only 9.2 months.
- HAART is thought to increase survival time by between 4 and 12 years.[8][9] This average reflects the fact that for some patients – and in many clinical cohorts this may be more than fifty percent of patients – HAART achieves far less than optimal results. This is due to a variety of reasons such as medication intolerance/side effects, prior ineffective antiretroviral therapy and infection with a drug-resistant strain of HIV.
- Non-adherence and non-persistence with antiretroviral therapy is the major reason most individuals fail to get any benefit from and develop resistance to HAART.[10]
- The side effects include lipodystrophy, dyslipidaemia, insulin resistance, an increase in cardiovascular risks and birth defects.[11][12]
Special Considerations
- HAART allows the stabilization of the patient’s symptoms and viremia, but it neither cures the patient of HIV, nor alleviates the symptoms, and high levels of HIV-1, often HAART resistant, return once treatment is stopped.[13][14] Moreover, it would take more than the lifetime of an individual to be cleared of HIV infection using HAART.[15] Despite this, many HIV-infected individuals have experienced remarkable improvements in their general health and quality of life, which has led to the plummeting of HIV-associated morbidity and mortality.[16][17][18]
HIV in children
Because HIV disease progression in children is more rapid than in adults, and laboratory parameters are less predictive of risk for disease progression, particularly for young infants, treatment recommendations are more aggressive for children than for adults.[19]
Alternate Therapies
Various forms of alternative medicine have been used to treat symptoms or alter the course of the disease.[20] In the first decade of the epidemic when no useful conventional treatment was available, a large number of people with AIDS experimented with alternative therapies. The definition of "alternative therapies" in AIDS has changed since that time. Then, the phrase often referred to community-driven treatments, untested by government or pharmaceutical company research, that some hoped would directly suppress the virus or stimulate immunity against it. Examples of alternative medicine that people hoped would improve their symptoms or their quality of life include massage, stress management, herbal and flower remedies such as boxwood,[21][22] and acupuncture;[20] when used with conventional treatment, many now refer to these as "complementary" approaches. Despite the widespread use of complementary and alternative medicine by people living with HIV/AIDS, the effectiveness of these therapies has not been established.[23]
Treatment Adherence
Adherence is taking the correct dose of each anti-HIV medication at the correct time and exactly as prescribed. Adherence is very important for successful HIV treatment. The reasons for non-adherence and non-persistence with HAART are varied and overlapping. Major psychosocial issues, such as poor access to medical care, inadequate social supports, psychiatric disease and drug abuse contribute to non-adherence. The complexity of these HAART regimens, whether due to pill number, dosing frequency, meal restrictions or other issues, along with side effects that create intentional non-adherence, also has a weighty impact.[24][25][26]
Difficulty in adherence
There are several reasons why adhering to an HIV treatment regimen can be diicult. Most treatment regimens involve taking several pills every day with or without food, or before or after other medications. Other factors that can make treatment adherence diicult include:
- Diiculty taking medications (such as trouble swallowing pills).
- Side efects from medications (for example, fatigue or diarrhea).
- Daily schedule issues (including a busy schedule, shift work, or travel away from home) .
- Being sick or depressed .
- Alcohol or drug abuse.
Importance of adherence
Adherence afects the success of HIV treatment in two ways:
- Good adherence to an HIV treatment regimen helps anti-HIV medications work efectively to reduce the viral load. Skipping medications, even occasionally, gives HIV to multiply rapidly. Preventing the virus from multiplying is the best way to stay healthy.
- Good adherence to an HIV treatment regimen also helps prevent drug resistance. One or more anti-HIV medications in a treatment regimen can become inefective as a result of drug resistance.
Skipping medications makes it easier for drug resistance to develop. HIV can develop resistance to the anti-HIV medications in a person’s current regimen or to other, similar anti-HIV medications not yet taken, limiting options for successful HIV treatment. And drug-resistant strains of HIV can be transmitted to others, too. Although there are many diferent anti-HIV medications and treatment regimens, studies show that a person’s first regimen ofers the best chance for long-term treatment success. Adhering to the regimen from the start will help ensure that the HIV treatment is successful.
Patient monitoring during antiretroviral therapy
A patient monitoring system is the backbone of clinical care, treatment and prevention by the clinical team caring for groups of patients.
Visit Frequency
Patients who are started on ART should generally have follow-up within one to two weeks. Patient should be asked about the following:
- Adverse effects.
- Adherence.
- Prevention of transmission.
See Also
References
- ↑ "The Relationship Between the Human Immunodeficiency Virus and the Acquired Immunodeficiency Syndrome". NIAID. Retrieved 2008-03-10.
- ↑ Sterne JA, Hernán MA, Ledergerber B, Tilling K, Weber R, Sendi P, Rickenbach M, Robins JM, Egger M (2005). "Long-term effectiveness of potent antiretroviral therapy in preventing AIDS and death: a prospective cohort study". Lancet. 366 (9483): 378–84. doi:10.1016/S0140-6736(05)67022-5. PMID 16054937. Retrieved 2012-02-15.
- ↑ Thompson MA, Aberg JA, Cahn P, Montaner JS, Rizzardini G, Telenti A, Gatell JM, Günthard HF, Hammer SM, Hirsch MS, Jacobsen DM, Reiss P, Richman DD, Volberding PA, Yeni P, Schooley RT (2010). "Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA panel". JAMA. 304 (3): 321–33. doi:10.1001/jama.2010.1004. PMID 20639566. Retrieved 2012-02-15. Unknown parameter
|month=ignored (help) - ↑ Shafer RW, Smeaton LM, Robbins GK, De Gruttola V, Snyder SW, D'Aquila RT, Johnson VA, Morse GD, Nokta MA, Martinez AI, Gripshover BM, Kaul P, Haubrich R, Swingle M, McCarty SD, Vella S, Hirsch MS, Merigan TC (2003). "Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection". N. Engl. J. Med. 349 (24): 2304–15. doi:10.1056/NEJMoa030265. PMID 14668456. Retrieved 2012-02-16. Unknown parameter
|month=ignored (help) - ↑ Puls RL, Srasuebkul P, Petoumenos K, Boesecke C, Duncombe C, Belloso WH, Molina JM, Li L, Avihingsanon A, Gazzard B, Cooper DA, Emery S (2010). "Efavirenz versus boosted atazanavir or zidovudine and abacavir in antiretroviral treatment-naive, HIV-infected subjects: week 48 data from the Altair study". Clin. Infect. Dis. 51 (7): 855–64. doi:10.1086/656363. PMID 20735258. Retrieved 2012-02-16. Unknown parameter
|month=ignored (help) - ↑ "A Pocket Guide to Adult HIV/AIDS Treatment February 2006 edition". Department of Health and Human Services. February 2006. Retrieved 2006-09-01.
- ↑ "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents" (PDF). Department of Health and Human Services Panel on Clinical Practices for Treatment of HIV Infection. 2005-10-06. Retrieved 2006-01-17.
- ↑ King JT, Justice AC, Roberts MS, Chang CH, Fusco JS and the CHORUS Program Team (2003). "Long-Term HIV/AIDS Survival Estimation in the Highly Active Antiretroviral Therapy Era". Medical Decision Making. 23 (1): 9&ndash, 20. PMID 12583451.
- ↑ Tassie JM, Grabar S, Lancar R, Deloumeaux J, Bentata M, Costagliola D and the Clinical Epidemiology Group from the French Hospital Database on HIV (2002). "Time to AIDS from 1992 to 1999 in HIV-1-infected subjects with known date of infection". Journal of acquired immune deficiency syndromes. 30 (1): 81&ndash, 7. PMID 12048367.
- ↑ Becker SL, Dezii CM, Burtcel B, Kawabata H, Hodder S. (2002). "Young HIV-infected adults are at greater risk for medication nonadherence". MedGenMed. 4 (3): 21. PMID 12466764.
- ↑ Montessori V, Press N, Harris M, Akagi L, Montaner JS (2004). "Adverse effects of antiretroviral therapy for HIV infection". CMAJ. 170 (2): 229&ndash, 238. PMID 14734438.
- ↑ Saitoh A, Hull AD, Franklin P, Spector SA (2005). "Myelomeningocele in an infant with intrauterine exposure to efavirenz". J. Perinatol. 25 (8): 555&ndash, 556. doi:10.1038/sj.jp.7211343. PMID 16047034.
- ↑ Martinez-Picado J, DePasquale MP, Kartsonis N; et al. (2000). "Antiretroviral resistance during successful therapy of human immunodeficiency virus type 1 infection". Proc. Natl. Acad. Sci. U. S. A. 97 (20): 10948&ndash, 10953. PMID 11005867.
- ↑ Dybul M, Fauci AS, Bartlett JG, Kaplan JE, Pau AK; Panel on Clinical Practices for Treatment of HIV. (2002). "Guidelines for using antiretroviral agents among HIV-infected adults and adolescents". Ann. Intern. Med. 137 (5 Pt 2): 381&ndash, 433. PMID 12617573.
- ↑ Blankson JN, Persaud D, Siliciano RF (2002). "The challenge of viral reservoirs in HIV-1 infection". Annu. Rev. Med. 53: 557&ndash, 593. PMID 11818490.
- ↑ Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD (1998). "Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection". N. Engl. J. Med. 338 (13): 853&ndash, 860. PMID 9516219.
- ↑ Wood E, Hogg RS, Yip B, Harrigan PR, O'Shaughnessy MV, Montaner JS (2003). "Is there a baseline CD4 cell count that precludes a survival response to modern antiretroviral therapy?". AIDS. 17 (5): 711&ndash, 720. PMID 12646794.
- ↑ Chene G, Sterne JA, May M, Costagliola D, Ledergerber B, Phillips AN, Dabis F, Lundgren J, D'Arminio Monforte A, de Wolf F, Hogg R, Reiss P, Justice A, Leport C, Staszewski S, Gill J, Fatkenheuer G, Egger ME and the Antiretroviral Therapy Cohort Collaboration (2003). "Prognostic importance of initial response in HIV-1 infected patients starting potent antiretroviral therapy: analysis of prospective studies". Lancet. 362 (9385): 679&ndash, 686. doi:10.1016/S0140-6736(03)14229-8. PMID 12957089.
- ↑ "Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection" (PDF). Department of Health and Human Services Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children. 2005-11-03. Retrieved 2006-01-17.
- ↑ 20.0 20.1 Saltmarsh S (2005). "Voodoo or valid? Alternative therapies benefit those living with HIV". Positively Aware. 3 (16): 46. PMID 16479668.
- ↑ Pharo A; et al. (1996). "Evaluation of the safety and efficacy of SPV-30 (boxwood extract) in patients with HIV disease". Int Conf AIDS (Jul 7–12): 11:19. abstract no. Mo. B.180.
- ↑ Durant J; et al. (1998). "Efficacy and safety of Buxussempervirens L. preparations (SPV-30) in HIV infected asymptomatic patients: a multi-centre, randomized, double-blind, placebo-controlled trial". Phytomedicine (5): 1–10.
- ↑ Mills E, Wu P, Ernst E (2005). "Complementary therapies for the treatment of HIV: in search of the evidence". Int. J. STD AIDS. 16 (6): 395&ndash, 403. PMID 15969772.
- ↑ Nieuwkerk P, Sprangers M, Burger D, Hoetelmans RM, Hugen PW, Danner SA, van Der Ende ME, Schneider MM, Schrey G, Meenhorst PL, Sprenger HG, Kauffmann RH, Jambroes M, Chesney MA, de Wolf F, Lange JM and the ATHENA Project (2001). "Limited Patient Adherence to Highly Active Antiretroviral Therapy for HIV-1 Infection in an Observational Cohort Study". Arch. Intern. Med. 161 (16): 1962&ndash, 1968. PMID 11525698.
- ↑ Kleeberger C, Phair J, Strathdee S, Detels R, Kingsley L, Jacobson LP (2001). "Determinants of Heterogeneous Adherence to HIV-Antiretroviral Therapies in the Multicenter AIDS Cohort Study". J. Acquir. Immune Defic. Syndr. 26 (1): 82&ndash, 92. PMID 11176272.
- ↑ Heath KV, Singer J, O'Shaughnessy MV, Montaner JS, Hogg RS (2002). "Intentional Nonadherence Due to Adverse Symptoms Associated With Antiretroviral Therapy". J. Acquir. Immune Defic. Syndr. 31 (2): 211&ndash, 217. PMID 12394800.